The present invention relates to the use of bromelain and components thereof for the manufacture of a medicament for increasing the IL-8 level in an individual so as to reduce or prevent inflammatory diseases in said individual and to use it as an adjuvant therapy to promote wound healing processes.
Inflammation, or the inflammatory process, respectively involves several biological reactions, proceeding in three successive phases: the degenerative phase, the vascular phase, and the healing phase.
In the degenerative phase, the affected cells become swollen. The cytoplasma of affected cells becomes vacuolized and an enlargement and fragmentation of cell nuclei can be observed. As some of the platelets in the damaged blood vessels disintegrate, mediators acting on sympathetic nerve endings are released.
Subsequently, in the vascular phase changes in the blood vessels can be observed. In particular, an extensive migration and activity of so-called inflammatory cells (granulocytes, particularly neutrophils, lymphocytes, macrophages and monocytes) and clearing of cellular debris and degenerated cells occur during this phase. As the capillary network and the postcapillary venules become flooded, congested and engorged by blood in active hyperemia and as a number of capillaries proliferate, a reddish appearance of inflamed tissue results.
In the last phase, the healing phase, the inflammation begins to subside and repair of wound starts.
Often inflammatory processes result in the formation of oedema, an accumulation of liquid in inter-tissue spaces, as the transport activity with respect to osmotic active compounds is locally decreased in the inflamed areas. Closely related to this phenomenon are swellings observed after operations or traumata, often causing considerable pain to the patient.
On a molecular basis, a plethora of active mediators are involved in the development of inflammation, such as e.g. cytokines and in particular interleukin 1-α, interleukin 1-β, interleukin 6, tumor necrosis factor α and β, interleukin 8 (IL-8).
In particular, IL-8 has been found to attract granulocytes and neutrophils towards an inflamed area and to activate the functional capacities of granulocytes, such as phagocytosis, cytotoxicity, chemotaxis etc. IL-8 is a non-glycosylated protein of 8 kDa having 72 amino acids and is also known as ANAP (anionic neutrophil activating peptide), GCP (granulocyte chemotactic peptide), LCF (lymphocyte chemotactic factor) and LIF (leukocyte inhibitory factor). IL-8 is produced in various cells e.g. monocytes/macrophages, granulocytes, T-cells, fibroblasts or endothelium cells as response to proinflammatory stimuli, such as IL-1, TNF, LPS and viruses.
Conventionally, the treatment of inflammatory conditions and oedema utilized an oral administration of non-steroidal anti-inflammatory drugs (NSAIDS), such as e.g. acetylsalicylic acid, phenylbutazone, diclofenac or indometacine. However, these agents exhibit several, sometimes severe secondary effects, e.g. gastrointestinal problems and adverse effects on gastro-enteric mucosa.
To overcome these drawbacks the art provided additional agents for treating inflammation. In this respect the WO 98/13057 discloses the use of a composition containing a Tripterygium wilfordii Hook F root preparation that has anti-inflammatory properties. Yet, since this composition also exhibits immunosuppressive activity the effect thereof in treating inflammation was rather poor. Further, in EP 100 94 04 the use of pADPRT (poly-ADP ribose polymerase) inhibitory compounds are proposed for the treatment of inflammatory diseases. However, also in this case unwanted secondary effects occur upon administration.
Therefore, there is a need in art for additional, well tolerated agents for treating inflammatory diseases and/or inflammatory diseases that do not show unwanted side effects.